Association of culprit plaque enhancement ratio, hypoperfusion and HbA1c with recurrent ischemic stroke in patients with atherosclerotic stenosis of the middle cerebral artery.

PURPOSE: To investigate the differences in intracranial culprit plaque characteristics of the middle cerebral artery (MCA), collateral circulation and hypoperfusion in patients with and without recurrent ischemic stroke and to identify the association with the recurrent ischemic cerebrovascular events. METHOD: Eighty-six patients with acute/subacute ischemic stroke caused by atherosclerotic plaques of the MCA were retrospectively enrolled and grouped into patients with recurrence (n = 36) and without recurrence (n = 50). All patients underwent high-resolution vessel wall imaging and dynamic susceptibility contrast-enhanced perfusion weighted imaging. The differences in culprit plaque characteristics, collateral circulation and hypoperfusion in the territory of the stenotic MCA were assessed between the two groups. The relationship between plaque characteristics and hypoperfusion was evaluated. The independent factors of recurrent ischemic stroke were identified by logistic regression analyses. RESULTS: Higher HbA1c, culprit plaque enhancement grade, culprit plaque enhancement ratio, and lower time to peak map based on the Alberta Stroke Program Early CT score (TTP-ASPECTS) were observed in the recurrence group(all p < 0.050). Both plaque enhancement grade and enhancement ratio were significantly associated with TTP-ASPECTS (p = 0.030 and 0.039, respectively). HbA1c, culprit plaque enhancement ratio and TTP-ASPECTS were independent factors of the recurrence of ischemic stroke (all p < 0.050). The area under the curve of the combination including the above factors (AUC = 0.819) was significantly higher than that of any variable alone after adjustment (all p < 0.050). CONCLUSIONS: Culprit plaque enhancement ratio, TTP-ASPECTS and HbA1c were independent factors of recurrent ischemic stroke. Their combination improved the accuracy in identifying the risk of recurrent ischemic stroke.

Pd-NHC catalysed regioselective activation of B(3,6)-H of o-carborane - a synergy between experiment and theory.

Regioselective B-H activation of o-carboranes is an effective way for constructing o-carborane derivatives, which have broad applications in medicine, catalysis and the wider chemical industry. However, the mechanistic basis for the observed selectivities remains unresolved. Herein, a series of density functional theory (DFT) calculations were employed to characterise the palladium N-heterocyclic carbene (Pd-NHC) catalysed regioselective B(3,6)-diarylation of o-carboranes. Computational results at the IDSCRF(ether)-LC-ωPBE/BS1 and IDSCRF(ether)-LC-ωPBE/BS2 levels showed that the reaction undergoes a Pd(0) → Pd(II) → Pd(0) oxidation/reduction cycle, with the regioselective B(3)-H activation being the rate-determining step (RDS) for the full reaction profile. The computed RDS free energy barrier of 24.3 kcal mol-1 agrees well with the 82% yield of B(3,6)-diphenyl-o-carborane in ether solution at 298 K after 24 hours of reaction. The Ag2CO3 additive was shown to play a crucial role in lowering the RDS free energy barrier and facilitating the reaction. Natural charge population (NPA) and molecular surface electrostatic potential (ESP) analyses successfully predicted the experimentally observed regioselectivities, with electronic effects being revealed to be the dominant contributors to product selectivity. Steric hindrance was also shown to impact the reaction rate, as revealed by experimental and computational characterisation studies of substituents and ligand effects. Furthermore, computational predictions aligned with the experimental findings that NHC ligands outperform the phosphine ones for this particular reaction. Overall, the observed trends reported in this work are expected to assist in the rational optimisation of the efficiency and regioselectivity of this and related reactions.

Interactions between the Astrocytic Volume-Regulated Anion Channel and Aquaporin 4 in Hyposmotic Regulation of Vasopressin Neuronal Activity in the Supraoptic Nucleus.

We assessed interactions between the astrocytic volume-regulated anion channel (VRAC) and aquaporin 4 (AQP4) in the supraoptic nucleus (SON). Acute SON slices and cultures of hypothalamic astrocytes prepared from rats received hyposmotic challenge (HOC) with/without VRAC or AQP4 blockers. In acute slices, HOC caused an early decrease with a late rebound in the neuronal firing rate of vasopressin neurons, which required activity of astrocytic AQP4 and VRAC. HOC also caused a persistent decrease in the excitatory postsynaptic current frequency, supported by VRAC and AQP4 activity in early HOC; late HOC required only VRAC activity. These events were associated with the dynamics of glial fibrillary acidic protein (GFAP) filaments, the late retraction of which was mediated by VRAC activity; this activity also mediated an HOC-evoked early increase in AQP4 expression and late subside in GFAP-AQP4 colocalization. AQP4 activity supported an early HOC-evoked increase in VRAC levels and its colocalization with GFAP. In cultured astrocytes, late HOC augmented VRAC currents, the activation of which depended on AQP4 pre-HOC/HOC activity. HOC caused an early increase in VRAC expression followed by a late rebound, requiring AQP4 and VRAC, or only AQP4 activity, respectively. Astrocytic swelling in early HOC depended on AQP4 activity, and so did the early extension of GFAP filaments. VRAC and AQP4 activity supported late regulatory volume decrease, the retraction of GFAP filaments, and subside in GFAP-VRAC colocalization. Taken together, astrocytic morphological plasticity relies on the coordinated activities of VRAC and AQP4, which are mutually regulated in the astrocytic mediation of HOC-evoked modulation of vasopressin neuronal activity.

Bioinformatics identify the role of chordin-like 1 in thyroid cancer.

The abnormal expression of chordin-like 1 (CHRDL1) is identified in many cancers, while the effect of CHRDL1 in thyroid cancer (THCA) remains unclear. The University of California Santa Cruz, Gene Expression Profiling Interactive Analysis, University of Alabama at Birmingham Cancer, and Gene Expression Omnibus database (GSE33570, GSE33630, and GSE60542) were used for determining the mRNA and methylation expression of CHRDL1 in tumor and normal tissues. Human Protein Atlas was used for exploring the protein expression level of CHRDL1. The genes correlated to CHRDL1 were assessed by cBioPortal database. The prognostic value of CHRDL1 was evaluated through Kaplan-Meier method, cox regression, and nomogram analysis. Kyoto Encyclopedia of Genes and Genomes, Gene Ontology, and gene set enrichment analysis were used for predicting potential function of CHRDL1. The relationship between CHRDL1 and immune cell infiltration was determined by Pearson method. The downregulated mRNA and protein expressions of CHRDL1 were identified in THCA through the analysis of data from The Cancer Genome Atlas, Gene Expression Omnibus, and Human Protein Atlas database. The survival analysis showed that the CHRDL1 expression significantly affected disease-free interval (DFI) and progression-free interval, and CHRDL1 was an independent predictor of DFI. Besides, we found that C-C motif chemokine ligand 21 could significantly affect DFI time when it was co-expressed with CHRDL1. Additionally, the function of CHRDL1 was enriched in cell migration, apoptosis, and immune cell receptor. The downregulated expression of CHRDL1 was observed in THCA and caused poor prognosis. CHRDL1 may be involved in signal pathway related to cancer development and immune response, which suggested it could be a potential biomarker.

Association of pre-diabetes and type 2 diabetes mellitus with intracranial plaque characteristics in patients with acute ischemic stroke.

OBJECTIVES: To investigate the association of pre-diabetes(i.e., the early stages of glucometabolic disturbance) and Type 2 diabetes mellitus (T2DM) with intracranial plaque characteristics in patients with acute ischemic stroke using three-dimensional high-resolution MR imaging. METHODS: One hundred and forty-three symptomatic patients with acute ischemic stroke attribute to intracranial atherosclerotic plaque were prospectively enrolled. All participants were further divided into three groups: normal glucose metabolism(non-diabetes) group(n = 41), pre-diabetes group(n = 45), and T2DM group(n = 57) according to glucometabolic status. Culprit plaque characteristics (such as plaque burden, normalized wall index and enhancement ratio), total plaque number, and global plaque enhancement score were analyzed and compared among the three glucometabolic groups. The association between pre-diabetes and T2DM with intracranial plaque characteristics was assessed by logistic regression and multivariate linear regression. RESULTS: Plaque number was higher in patients with pre-diabetes and T2DM compared with those with non-diabetes(3.71 ± 1.83 and 3.75 ± 1.71 vs 2.24 ± 1.46, p = 0.006). Multivariate logistic regression showed a significant association of multiple intracranial plaques with pre-diabetes(OR 3.524, 95% CI 1.082 ~ 11.479, p = 0.037), T2DM(OR 3.760, 95% CI 1.098 ~ 12.872, p = 0.035) and luminal stenotic rate. Both pre-diabetes and T2DM were significantly associated with culprit plaque enhancement ratio(ß = 0.527 and ß = 0.536; respectively; p < 0.001) and global plaque enhancement score(ß = 0.264 and ß = 0.373; respectively; p < 0.05). CONCLUSIONS: Patients with pre-diabetes and T2DM had similar intracranial atherosclerotic plaque vulnerability, as demonstrated by multiple plaques, increased culprit plaque enhancement ratio and global plaque enhancement score. ADVANCES IN KNOWLEDGE: Pre-diabetes might be a risk factor for intracranial plaque vulnerability. It is necessary to monitor a slight increase in blood glucose in non-diabetes patients with acute ischemic stroke.

Magnetic-assisted laparoscopic liver transplantation in swine.

BACKGROUND: Although laparoscopic technology has achieved rapid development in the surgical field, it has not been applied to liver transplantation, primarily because of difficulties associated with laparoscopic vascular anastomosis. In this study, we introduced a new magnetic-assisted vascular anastomosis technique and explored its application in laparoscopic liver transplantation in pigs. METHODS: Two sets of magnetic vascular anastomosis rings (MVARs) with different diameters were developed. One set was used for anastomosis of the suprahepatic vena cava (SHVC) and the other set was used for anastomosis of the infrahepatic vena cava (IHVC) and portal vein (PV). Six laparoscopic orthotopic liver transplantations were performed in pigs. Donor liver was obtained via open surgery. Hepatectomy was performed in the recipients through laparoscopic surgery. Anastomosis of the SHVC was performed using hand-assisted magnetic anastomosis, and the anastomosis of the IHVC and PV was performed by magnetic anastomosis with or without hand assistance. RESULTS: Liver transplants were successfully performed in five of the six cases. Postoperative ultrasonographic examination showed that the portal inflow was smooth. However, PV bending and blood flow obstruction occurred in one case because the MVARs were attached to each other. The durations of loading of MVAR in the laparoscope group and manual assistance group for IHVC and PV were 13 ± 5 vs. 5 ± 1 min (P < 0.01) and 10 ± 2 vs. 4 ± 1 min (P < 0.05), respectively. The durations of MVAR anastomosis in the laparoscope group and manual assistance group for IHVC and PV were 5 ± 1 vs. 1 ± 1 min (P < 0.01), and 5 ± 1 vs. 1 ± 1 min (P < 0.01), respectively. The anhepatic phase was 43 ± 4 min in the laparoscope group and 23 ± 2 min in the manual assistance group (P < 0.01). CONCLUSIONS: Our study showed that magnetic-assisted laparoscopic liver transplantation can be successfully carried out in pigs.

Association of trimethylamine N-Oxide with cardiovascular and all-cause mortality in hemodialysis patients.

BACKGROUND: Trimethylamine-N-Oxide (TMAO) is a proatherogenic and prothrombotic metabolite. Our study examined the association of plasma TMAO level with cardiovascular and all-cause mortality in hemodialysis (HD) patients. METHODS: Patients who were at least 18 years-old and received HD for at least 6 months were enrolled within 6 months. Patients with coronary heart disease, congestive heart failure, arrhythmia, or stroke within 3 months before study onset were excluded. The primary endpoints were cardiovascular and all-cause death, and the secondary endpoint was cerebrovascular death. RESULTS: We recruited 252 patients and divided them into a high-TMAO group (>4.73 µg/mL) and a low-TMAO group (≤4.73 µg/mL). The median follow-up time was 73.4 months (interquartile range: 42.9, 108). A total of 123 patients died, 39 from cardiovascular disease, 19 from cerebrovascular disease, and 65 from other causes. Kaplan-Meier analysis indicated that the high-TMAO group had a greater incidence of cardiovascular death (Log-Rank: p = 0.006) and all-cause death (Log-Rank: p < 0.001). Cox regression analysis showed that high TMAO level was significantly associated with cardiovascular and all-cause mortality. After adjustment for confounding, this association remained significant for cardiovascular mortality (TMAO as a continuous variable: HR: 1.18, 95%CI: 1.07, 1.294, p < 0.001; TMAO as a dichotomous variable: HR: 3.44, 95%CI: 1.68, 7.08, p < 0.001) and all-cause mortality (TMAO as a continuous variable: HR: 1.14, 95%CI: 1.08, 1.21, p < 0.001; TMAO as a dichotomous variable: HR: 2.54, 95%CI: 1.71, 3.76, p < 0.001). CONCLUSIONS: High plasma TMAO level is significantly and independently associated with cardiovascular and all-cause mortality in HD patients.

Operation start time and long-term outcome of hepatocellular carcinoma after curative hepatic resection.

PURPOSE: The objective of the current study was to examine the potential effects of surgery start times (morning vs. afternoon) on the long-term prognosis of patients after hepatic resection (HR) for hepatocellular carcinoma (HCC). METHODS: All eligible patients were divided into 2 groups according to the start time of surgery: group M (morning surgery, 8 AM-1 PM) and group A (afternoon surgery, 1 PM-6 PM). Clinicopathologic and surgical parameters, as well as oncologic outcomes were compared between the 2 groups. RESULTS: In total, 231 patients were included in the study. There was no difference in age, body mass index, comorbidities, tumor size, tumor location, tumor stages, surgical procedures, or surgical margin between morning and afternoon surgery (all P > 0.05). In contrast, patients in group M experienced longer operation duration than those in group A (median, 240 minutes vs. 195 minutes, P = 0.004). However, no differences of overall survival were observed between morning and afternoon surgery groups in the whole cohort or stratified by surgical margin (all P > 0.05). CONCLUSION: Surgery start times during the work day have no measurable influence on patient outcome following curative HR for HCC, indicating good self-regulation and professional judgment of surgeons for progressive fatigue during surgery.

miR-92b promotes gastric cancer growth by activating the DAB2IP-mediated PI3K/AKT signalling pathway.

OBJECTIVES: miR-92b has been reported to play critical roles in several carcinomas; however, our understanding of the mechanisms by which miR-92b stimulates gastric cancer (GC) is incomplete. The aim of this study was to investigate the clinical significance and functional relevance of miR-92b in GC. MATERIALS AND METHODS: Expression of miR-92b in GC and peritumoural tissues was determined using qRT-PCR, in situ hybridization and bioinformatics. CCK-8, colony formation and fluorescence-activated cell sorting assays were utilized to explore the effect of miR-92b on GC cells. A luciferase reporter assay and Western blotting were employed to verify miR-92b targeting of DAB2IP. Furthermore, Western blotting was used to evaluate the levels of DAB2IP and PI3K/Akt signalling pathway-related proteins. RESULTS: In this study, we found that miR-92b was upregulated in GC tissues compared with peritumoural tissues. Overexpression of miR-92b promoted cell proliferation, colony formation, and G0 /G1 transition and decreased apoptosis. Our results indicated that miR-92b repressed the expression of DAB2IP and that loss of DAB2IP activated the PI3K/AKT signalling pathway. Overexpression of DAB2IP rescued the effects of miR-92b in GC cells. Finally, our results demonstrated a significant correlation between miR-92b expression and DAB2IP expression in GC tissues. CONCLUSIONS: Our results suggest that miR-92b promotes GC cell proliferation by activating the DAB2IP-mediated PI3K/AKT signalling pathway. The miR-92b/DAB2IP/PI3K/AKT signalling axis may be a potential therapeutic target to prevent GC progression.

Analysis on the factors that influence the treatment outcome of Tibetan nationality new smear-positive pulmonary tuberculosis patients in Qinghai Province / 中华疾病控制杂志

@#Objective To analyze the treatment outcome and related influencing factors of Tibet- an nationality new smear-positive pulmonary tuberculosis patients in Qinghai Province，so as to provide evidence for tuberculosis control and treatment among Tibetan population． Methods Statistical analysis was conducted on 5 564 Tibetan nationality new smear-positive pulmonary tuberculosis cases in Qinghai province who were reported in the China Tuberculosis Information Management System and approved to receive treatment from 2008 to 2017． The main influencing factors were detected by unconditional Logistic regression model analysis，dependent variable was successful treatment or not，independent variables were other factors related to the treatment outcome． Ｒesults The treatment success rate of Tibetan nationality new smear-positive pulmonary tuberculosis cases was 87. 1% ( 4 848 /5 564) ，and the adverse outcome rate was 12. 9% ( 716 /5 564) ． Unconditional Logistic regression model analysis indicated that non-full- course supervision management，living in agricultural and pastoral area，having severe disease，floating population，and age older than 60 years were risk factors of adverse outcome． The odds ratio( OＲ) 95% confidence interval( CI) of the above risk factors were 13. 044( 10. 671-15. 944) ，2. 305( 1. 703-3. 119) ， 2. 090( 1. 346-3. 243) ，1. 967( 1. 443-2. 682) ，and 1. 909( 1. 410-2. 586) ． Clinical consultation，farmers and herdsmen were protective factors． The OＲ( 95% CI) were 0. 451( 0. 375-0. 543) ，and 0. 786( 0. 627- 0. 985) ． Conclusions Treatment success rate of Tibetan nationality new smear positive pulmonary tuberculosis cases was low． Therefore，the directly observed treatment short-course ( DOTS) strategy should be strictly implemented and the full-course supervision management should be strengthened to improve the treatment success rate． More attention should be paid to the elderly，severe，floating，agricultural and pastoral populations among the Tibetan population．

Cortactin promotes colon cancer progression by regulating ERK pathway.

Cortactin is upregulated in various cancers including breast cancer, head and neck squamous cell carcinoma and gastric cancer. However, the role of cortactin in the pathogenesis of colon cancer remains unclear. mRNA expression of cortactin in colon cancer samples and cell lines was detected by quantitative real-time PCR (qRT-PCR), while protein expression of cortactin in colon cancer tissues and adjacent non-cancer tissues was assessed by immunohistochemistry. The role of cortactin in regulation of the proliferation of colon cancer derived cells were investigated both in vitro and in vivo. In the total of 60 paired colon cancer specimens, compared with the adjacent non-cancer tissues, the expression of cortactin mRNA was upregulated in 45 (75.0%). Immunohistochemical analysis showed significantly increased cortactin expression in colon cancer (42/60, 70.0%) compared to control tissues (18/60, 30.0%). Overexpression of cortactin promoted HCT116 cellular colony formation and tumor growth. Conversely, cortactin knockdown inhibited these effects in SW480 cells. Mechanistic analyses indicated that cortactin was able to activate the EGFR-ERK signaling pathway. Additionally, cortactin expression was associated with tumor size, tumor stages and lymphatic invasion, increased cortactin expression predicts poor prognosis in patients with colon cancer. In summary, cortactin demonstrated the promotive effect in human colon cancer cell growth and tumorigenicity. These results indicated that cortactin may serve as an effective target for gene therapy.

High-resolution modeling of isotachophoresis and zone electrophoresis.

The space-time conservation element and solution element (CESE) method is applied to simulate the ITP and zone electrophoresis (ZE) separation phenomena. The CESE method expresses the governing equation in the integral form of the conservation law, and has a second-order accuracy in both space and time. The current results show that the CESE solutions for the ITP and ZE phenomena are more accurate than those obtained using conventional numerical schemes, which are characterized by serious numerical diffusion and oscillation. Furthermore, the CESE method suppresses the numerical oscillations or peaks observed in the results obtained using traditional second-order finite difference schemes. Finally, the results reveal that the CESE method accurately models the sharp boundaries between adjacent ITP samples under steady-state conditions. Overall, the results presented in this study demonstrate the numerical accuracy of the CESE method and confirm its applicability to the modeling of a range of electrophoretic phenomena.

Evaluation of HCPTd1,d14-double passaged intervening chemotherapy protocol for hepatocellular carcinoma.

AIM: To establish a kind of standardization of the clinical chemotherapeutic prototypes for unresectable hepatocellular carcinomas (HCC). METHODS: 10-Hydroxycamptothecin (HCPT) was applied through transcatheter arterial embolization (TAE) to HCC patients who were categorized into three groups: (1) test group: treatment with HCPT twice (HCPT d1 and 14) through TAE and portal venous embolization. (2) Control I: treatment with anticancer drugs without HCPT. (3) Control II: treatment with HCPT as a major component in anticancer drugs once (HCPT d1). A set of comparisons between test groups and control I and II groups were performed before and after the treatment to study the effectiveness of each treatment, in terms of tumor volumes, dynamic variations in serum alpha-fetoprotein (AFP), gamma-glutamyl transferase hepatoma-specific band (GGT-II), patient survival and adverse events. RESULTS: The general effectiveness rate of the test group reached 62.1% (72/116), remarkably higher than that of control I (32.1%, 40/124) and control II (54.7%, 47/56), (P<0.01 and P<0.05, respectively). Especially, the reduction rate or disappearance of the portal vein tumor emboli was as high as 88.4% (61/69) in the test group, in contrast with 13.9% (10/72) in control I and 35.9% (18/51) in control II (P<0.01 and P<0.01, respectively). After treatment, AFP decreased or turned to negative levels at 52.3% (34/65) in control I, 67.3% (35/52) in control II, and 96.8% (60/62) in the test group. Also GGT-II declined or became negative at 37.8% (28/74) in control I, 69.5% (57/82) in control II, and 94.7% (89/94) in test group (P<0.01 and P<0.05, respectively). CONCLUSION: We have designed a good protocol (test group) to treat HCC with excellent advantages of high efficiency, low cost, low toxicity and low adverse events and easy application. It could be recommended as one of the standardizations for HCC treatment in clinical practice.